Jawaid Paras, Rehman Mati Ur, Zhao Qing-Li, Misawa Masaki, Ishikawa Kenji, Hori Masaru, Shimizu Tadamichi, Saitoh Jun-Ichi, Noguchi Kyo, Kondo Takashi
Department of Radiology, Graduate School of Medicine and Pharmaceutical Sciences University of Toyama, Toyama, Japan.
Theranostic Devices Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan.
Cell Death Discov. 2020 Sep 10;6:83. doi: 10.1038/s41420-020-00314-x. eCollection 2020.
Gold nanoparticles (Au-NPs) have attracted attention as a promising sensitizer owing to their high atomic number (Z), and because they are considered fully multifunctional, they are preferred over other metal nanoparticles. Cold atmospheric plasma (CAP) has also recently gained attention, especially for cancer treatment, by inducing apoptosis through the formation of reactive oxygen species (ROS). In this study, the activity of different sized Au-NPs with helium-based CAP (He-CAP) was analyzed, and the underlying mechanism was investigated. Treating cells with only small Au-NPs (2 nm) significantly enhanced He-CAP-induced apoptosis. In comparison, 40 nm and 100 nm Au-NPs failed to enhance cell death. Mechanistically, the synergistic enhancement was due to 2 nm Au-NPs-induced decrease in intracellular glutathione, which led to the generation of intracellular ROS. He-CAP markedly induced ROS generation in an aqueous medium; however, treatment with He-CAP alone did not induce intracellular ROS formation. In contrast, the combined treatment significantly enhanced the intracellular formation of superoxide (O) and hydroxyl radical (OH). These findings indicate the potential therapeutic use of Au-NPs in combination with CAP and further clarify the role of Au-NPs in He-CAP-aided therapies.
金纳米颗粒（Au-NPs）因其高原子序数（Z）而作为一种有前景的敏化剂受到关注，并且由于它们被认为具有完全的多功能性，所以比其他金属纳米颗粒更受青睐。冷大气等离子体（CAP）最近也受到关注，特别是在癌症治疗方面，它通过形成活性氧（ROS）诱导细胞凋亡。在本研究中，分析了不同尺寸的金纳米颗粒与氦基冷大气等离子体（He-CAP）的活性，并研究了其潜在机制。仅用小尺寸金纳米颗粒（2纳米）处理细胞显著增强了He-CAP诱导的细胞凋亡。相比之下，40纳米和100纳米的金纳米颗粒未能增强细胞死亡。从机制上讲，协同增强是由于2纳米金纳米颗粒诱导细胞内谷胱甘肽减少，从而导致细胞内ROS的产生。He-CAP在水介质中显著诱导ROS生成；然而，单独用He-CAP处理不会诱导细胞内ROS形成。相反，联合处理显著增强了细胞内超氧阴离子（O）和羟基自由基（OH）的形成。这些发现表明金纳米颗粒与冷大气等离子体联合使用具有潜在的治疗用途，并进一步阐明了金纳米颗粒在He-CAP辅助治疗中的作用。
